Project Summary/Abstract This amended R03 proposal is for a NIDA-sponsored, AIDS-Science Track Award for Research Transition (A- START; PA-15-290). The primary goal of the A-START program is to support the entry of new and early career investigators into the area of drug abuse research in HIV/AIDS, particularly those whose current research program focuses on either drug abuse or HIV/AIDS, and who now wish to expand their program and study the intersection of these two areas. The PI of the current proposal is an early career investigator who received his first R01 award in August 2014 for a multimodal neuroimaging study examining how HIV-infection modulates age-related cognitive decline. Since then, he has received an administrative supplement to expand enrollment and examine sex differences in the R01 project, and been involved in other successful grants as a co- investigator. The PI is strongly committed to a career in neuroAIDS research, and through an A-START will expand his research program into the neurobiology and neuropsychology of drug abuse in HIV/AIDS, with a long-term focus on how substance abuse affects the incidence and severity of HIV-associated neurocognitive disorders. Such disorders are the most common neurological complication of HIV disease, with prevalence estimates ranging from 35-70% of all HIV-infected patients, and research targeting such comorbidities has been identified as a top priority by the Office of AIDS Research (see NOT-OD-15-137). The primary research goals of this project are to quantify the unique neuropsychological and neurobiological consequences of chronic marijuana abuse in HIV-infected patients. To this end, we will study demographically- matched groups of HIV-infected and uninfected heavy, light, and non-users of marijuana. All participants will undergo neuropsychological testing, high-resolution structural neuroimaging, and dynamic functional imaging with magnetoencephalography (MEG). MEG is an emerging method that directly quantifies neurophysiological activity and can produce functional maps with high spatial precision and millisecond temporal resolution. Data for the HIV-infected and uninfected light and non-user groups will be collected through the PI?s R01 project, which uses the same neuropsychological and imaging methods, but considers heavy use to be an exclusion criteria. Importantly, only four studies have examined the impact of marijuana abuse on cognitive function in HIV-infected patients, and these studies reported mixed results. Further, no study to date has evaluated brain structure or function in this area. Thus, the consequences of marijuana abuse in HIV-infected patients remain largely unknown, which is especially concerning as we enter an era of marijuana legalization. In summary, this A-START project will: (a) provide seminal neuroimaging and neuropsychological data on how HIV-associated neurocognitive disorders may be affected by chronic marijuana use, (b) contribute novel insight into whether the severity of neurological complications connects with the extent of marijuana consumption (heavy vs. light), and (c) serve as a springboard for the PI to begin drug abuse research in HIV/AIDS.